The diagnostic accuracy of spirometry as screening tool for adult patients with a benign subglottic stenosis.

BACKGROUND: There is a considerable diagnostic delay in the diagnosis 'benign acquired subglottic stenosis in adults' (SGS, diagnosed by the reference standard, i.e. laryngo- or bronchoscopy). Patients are frequently misdiagnosed since symptoms of this rare disease may mimic symptoms of 'asthma.' The 'Expiratory Disproportion Index' (EDI) obtained by spirometry, may be a simple instrument to detect an SGS-patient. The aim of this study was to evaluate the diagnostic accuracy of the EDI in differentiating SGS patients from asthma patients. METHODS: We calculated the EDI from spirometry results of all SGS-patients in the Leiden University Medical Center (LUMC), who had not received treatment 2 years before their spirometry examination. We compared these EDI results with the EDI results of all true asthma patients between 2011 and 2019, who underwent a bronchoscopy (exclusion of SGS by laryngo- or bronchoscopy). RESULTS: Fifty patients with SGS and 32 true asthma patients were included. Median and IQR ranges of the EDI for SGS and asthma patients were 67.10 (54.33-79.18) and 37.94 (32.41-44.63), respectively. Area under the curve (ROC) of the accuracy of the EDI at discriminating SGS and asthma patients was 0.92 (95% CI = 0.86-0.98). The best cut-off point for the EDI was > 48 (i.e. possible upper airway obstruction), with a sensitivity of 88.0%% (95%CI = 77.2-95.0%%) and specificity of 84.4% (95%CI = 69.4-94.1%). CONCLUSIONS: The EDI has a good diagnostic accuracy discriminating subglottic stenosis patients from asthma patients, when compared to the reference standard. This measurement from spirometry may potentially shorten the diagnostic delay of SGS patients. Further studies are needed to evaluate clinical reproducibility.

Multidimensional assessment of voice quality after injection augmentation of the vocal fold with autologous adipose tissue or calcium hydroxylapatite.

PURPOSE: The purpose of this study was to evaluate short- and long-term outcome of injection augmentation with autologous adipose tissue (AAT) and calcium hydroxylapatite injection (CAHA) in patients with a unilateral vocal fold paralysis (UVFP). DESIGN/METHODS: A retrospective cohort study was performed in patients diagnosed with UVFP, who had received injection augmentation with AAT or CAHA. Multidimensional voice analysis was performed before, 3 and 12 months after injection. This analysis included patient self-assessment (Voice Handicap Index-30), perceptual (overall dysphonia grade according to the GRBAS scale), aerodynamic (MPT, s/z ratio) and acoustic (fundamental frequency, dynamic range) parameters. Effects were assessed using a linear mixed model analysis. RESULTS: Forty-six patients were available for evaluation, with a total of 53 injection augmentations (AAT n = 39; CAHA n = 14). We found significant improvement of patient self-assessment and perceptive voice outcome at 3 months, which were maintained at 12 months. In the CAHA group, s/z ratio and dynamic range of extreme frequencies also improved significantly over time. No statistically significant differences were found between the two treatments (AAT vs. CAHA). No major complications were reported. CONCLUSION: This study, using a guide-line recommended panel of outcome parameters, shows a high success rate of injection augmentation with AAT or CAHA for patients with UVFP at 12 months with significant improvement in most voice outcome parameters, although voices do not completely normalize. There is no significant difference in outcome between the two materials.

Long-term voice outcomes of laryngeal framework surgery for unilateral vocal fold paralysis.

OBJECTIVE: To evaluate the short- and long-term voice outcomes after unilateral medialization thyroplasty (MT) and unilateral medialization thyroplasty with arytenoid adduction (MT + AA) in patients with unilateral vocal fold paralysis. METHODS: Voice outcomes were assessed preoperatively, and postoperatively at 3 and 12 months according to a standardized protocol. Voice assessment was performed using Voice Handicap Index (VHI), GRBAS Grade, Maximum Phonation Time (MPT), s/z-ratio and subjective numeric rating scales on voice quality, effort, performance and influence on life. RESULTS: Sixty-one patients were included (34 MT and 27 MT + AA). Significant pre- to postoperative improvements were seen in all voice outcome parameters. No significant differences in post-operative values were identified between the groups. CONCLUSION: Based on our findings, we conclude that patients with unilateral vocal fold paralysis who undergo MT and MT + AA achieve comparable and significant long time voice improvement, although voices do not completely normalize. We also conclude that this does not mean that AA is a superfluous procedure, but can indicate the accurate identification of patients in need of the additional AA procedure based on clinical parameters.

Proposal for a Core Outcome Set of Measurement Instruments to Assess Quality of Voice in Adductor Spasmodic Dysphonia Based on a Literature Review.

OBJECTIVES: Uniform evaluation of treatment effect on the quality of voice in adductor spasmodic dysphonia (AdSD) is challenging due to the broad variety of available outcome measurement instruments (OMIs). The European Laryngological Society categorized five types of measurement domains for voice quality evaluations: patient-reported outcome measures, perceptual analyses, acoustic analyses, visual analyses, and aerodynamic measurements. The aim of this study was to propose a core outcome set (COS) for these domains, enabling systematic assessments of treatment effects on the quality of voice in patients with AdSD. METHODS: The PubMed, Embase, and Cochrane databases were searched for eligible studies published before July 2019. The results were systematically analyzed following the protocol of the COnsensus-based Standards for the selection of health Measurement INstruments/Core Outcome Measures in Effectiveness Trials initiative. The proposed COS is based on the prevalence of OMIs, quality of the included studies, criteria for good measurement properties, and correlations to other OMI domains. RESULTS: A total of 76 articles were included, with nearly all studies and OMIs found to be of moderate or low quality. The 19 studies that reported on the correlation of OMIs demonstrated conflicting results. Appraising the best available evidence, our proposed COS consisted of patient-reported outcome measures (voice handicap index), perceptual measurements (grade, roughness, breathiness, strain, and voice breaks) and acoustic measurements (voice breaks, voice onset time, aperiodicity, and multiparameter algorithms). CONCLUSION: A review of OMIs evaluating treatment effects in AdSD was conducted. Based on this review, a uniform COS was proposed. However, evidence for the selected instruments was limited. Further exploration into the validity and reliability of OMIs for AdSD is recommended.

Bilateral medialization thyroplasty in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate voice outcome after bilateral medialization thyroplasty in patients with non-paralytic glottic insufficiency due to vocal fold atrophy with or without sulcus. METHODS: Retrospective cohort study on 29 patients undergoing bilateral medialization thyroplasty for vocal fold atrophy (14 procedures) or atrophy with sulcus (15 procedures) between October 2012 and November 2017. Voice data were collected and analyzed for the preoperative and the 3- and 12-month postoperative time point according to a standardized protocol, including Voice Handicap Index (VHI)-30 and perceptual, acoustic and aerodynamic parameters. Failure rate was based on number of revisions within 12 months and non-relevant improvement (< 10 points) in VHI-30 at 12 months. RESULTS: There was a clinically relevant (≥ 15 points) and statistically significant improvement (p < 0.0001) in the VHI-30 (preoperative: 55.8 points; postoperative at 12 months: 30.9 points). Fundamental frequency for male subjects decreased significantly from 175 to 159 Hz (p = 0.0001). The pre- and post-operative grade of dysphonia was significantly lower in patients with atrophy compared to atrophy and sulcus (mean difference 0.70, p = 0.017). CONCLUSION: Bilateral medialization thyroplasty is a valid treatment option for patients with atrophy with or without sulcus. Outcomes are comparable to other methods reported in literature. However, there is a great need for larger, prospective studies with long-term follow-up to gain more insight into the comparative voice outcomes for the different forms of surgery for patients with glottic incompetence due to atrophy with or without sulcus.

Adductor spasmodic dysphonia: Botulinum toxin a injections or laser thyroarytenoid myoneurectomy? A comparison from the patient perspective.

OBJECTIVES/HYPOTHESIS: The current gold standard of therapy for adductor spasmodic dysphonia (AdSD) is injection of botulinum toxin A (BTX) in the adductor musculature. A surgical procedure could potentially offer more stable and long-lasting voice quality. In this study, we report the long-term results of endoscopic laser thyroarytenoid (TA) myoneurectomy versus BTX treatment in the same patients with AdSD. STUDY DESIGN: Retrospective case series. METHODS: Between July 2013 and September 2016, a total of 22 patients with AdSD were included. Voice outcomes were measured using the Voice Handicap Index and a Likert-scale patient-reported voice questionnaire. Data were obtained for each patient at four time points: preoperatively with and without BTX and twice postoperatively at 3 months (short term) and 12 months (long term). RESULTS: No statistically significant differences were found between voice outcome after BTX injection and the short- and long-term postoperative voice outcomes for the group as a whole. During postoperative follow-up, 10 of the 22 patients (45%) needed a second procedure after an average of 18 months (interquartile range, 13-22 months) due to recurrence of their original voice problem. CONCLUSIONS: The TA myoneurectomy showed encouraging results, comparable to BTX after follow-up of 12 months for the group as a whole. However, after good results initially, voice deterioration was seen in 45% of the patients who all underwent a second procedure. These preliminary results provide important insights into the value of TA myoneurectomy as a potential definite treatment for a select group of patients with AdSD. Further research might explore long-term results after revision surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:741-746, 2020.

Bilateral vocal fold injection with autologous fat in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate voice outcome after bilateral vocal fold injection with autologous fat in patients with non-paralytic glottic insufficiency due to vocal fold atrophy with or without sulcus. METHODS: This is a retrospective cohort study from September 2012 to December 2017 including 23 patients undergoing bilateral vocal fold injection with autologous fat (24 procedures) for vocal fold atrophy (15 procedures) or atrophy with sulcus (Ford type II or III) (9 procedures). Voice data were collected and analyzed for the preoperative and the 3- and 12-month postoperative time points according to a standardized protocol, including Voice Handicap Index (VHI)-30 and perceptive, acoustic and aerodynamic parameters. Failure rate was defined as non-relevant improvement (< 10 points) in VHI-30 at 12 months and number of revisions within 12 months. RESULTS: There was a clinically relevant (≥ 15 points) and statistically significant improvement in the VHI-30 (preoperative: 49.1 points; postoperative at 12 months: 29.7 points). Change in dynamic range was also statistically significant over time (p = 0.028). There were no differences in voice parameters between patients with atrophy only and atrophy with sulcus, although grade tended to be lower in patients with atrophy only over all time points. CONCLUSION: This study shows that bilateral vocal fold injection with autologous fat is a beneficial treatment not only for patients with atrophy but also for patients with sulcus. A comparison of the results with those reported from other forms of sulcus surgery confirmed this finding. However, there is a need for further prospective studies comparing the short- and long-term effects of different techniques.

Bilateral trial vocal fold injection with hyaluronic acid in patients with vocal fold atrophy with or without sulcus.

PURPOSE: To evaluate the outcome of bilateral trial vocal fold injection (VFI) with hyaluronic acid in patients with vocal fold atrophy ± sulcus and to assess the predictive value of trial VFI on the outcome of durable medialization procedure. METHODS: Voice data collected according to a standardized protocol before and one month after trial VFI of 68 patients with vocal fold atrophy (30) and atrophy with sulcus (38) were analyzed. Voice Handicap Index (VHI)-30 was compared to the outcome of a durable medialization at 3 and 12 months. RESULTS: The overall VHI-30 improvement was 16.8 points (from 49.9 to 33.1), which was statistically significant and clinically relevant. 57.8% of the patients experienced enough subjective benefit after trial VFI to undergo durable medialization. Of the patients that experienced subjective benefit 62% had a clinically relevant improvement in VHI-30. There was no relevant change in other parameters and no difference between ± sulcus. After durable medialization 90-94% of the patients had VHI-30 scores similar to or better than post-trial VFI. CONCLUSION: The majority of patients experience subjective improvement after bilateral trial VFI indicating that medialization is a valid treatment option for patients with vocal fold atrophy ± sulcus. The VHI-30 only partially overlaps with patients' subjective evaluation and does not predict which patients will experience subjective improvement. It is, however, predictive for VHI-30 outcome after durable medialization. The aerodynamic and acoustic parameters showed no relevant change. Further identification of voice assessment parameters accurately reflecting the subjective experience of these patients is warranted.

Whispering dysphonia (DYT4 dystonia) is caused by a mutation in the TUBB4 gene.

OBJECTIVE: A study was undertaken to identify the gene underlying DYT4 dystonia, a dominantly inherited form of spasmodic dysphonia combined with other focal or generalized dystonia and a characteristic facies and body habitus, in an Australian family. METHODS: Genome-wide linkage analysis was carried out in 14 family members followed by genome sequencing in 2 individuals. The index patient underwent a detailed neurological follow-up examination, including electrophysiological studies and magnetic resonance imaging scanning. Biopsies of the skin and olfactory mucosa were obtained, and expression levels of TUBB4 mRNA were determined by quantitative real-time polymerase chain reaction in 3 different cell types. All exons of TUBB4 were screened for mutations in 394 unrelated dystonia patients. RESULTS: The disease-causing gene was mapped to a 23cM region on chromosome 19p13.3-p13.2 with a maximum multipoint LOD score of 5.338 at markers D9S427 and D9S1034. Genome sequencing revealed a missense variant in the TUBB4 (tubulin beta-4; Arg2Gly) gene as the likely cause of disease. Sequencing of TUBB4 in 394 unrelated dystonia patients revealed another missense variant (Ala271Thr) in a familial case of segmental dystonia with spasmodic dysphonia. mRNA expression studies demonstrated significantly reduced levels of mutant TUBB4 mRNA in different cell types from a heterozygous Arg2Gly mutation carrier compared to controls. INTERPRETATION: A mutation in TUBB4 causes DYT4 dystonia in this Australian family with so-called whispering dysphonia, and other mutations in TUBB4 may contribute to spasmodic dysphonia. Given that TUBB4 is a neuronally expressed tubulin, our results imply abnormal microtubule function as a novel mechanism in the pathophysiology of dystonia.

Near-infrared fluorescence sentinel lymph node mapping of the oral cavity in head and neck cancer patients.

OBJECTIVES: Elective neck dissection is frequently performed during surgery in head and neck cancer patients. The sentinel lymph node (SLN) procedure can prevent the morbidity of a neck dissection and improve lymph node staging by fine pathology. Near-infrared (NIR) fluorescence imaging is a promising technique to identify the sentinel lymph node (SLN) intraoperatively. This feasibility study explored the use of indocyanine green adsorbed to human serum albumin (ICG:HSA) for SLN mapping in head and neck cancer patients. MATERIALS AND METHODS: A total of 10 consecutive patients with oral cavity or oropharyngeal cancer and a clinical N0 neck were included. After exposure of the neck, 1.6 mL of ICG:HSA (500 µM) was injected at four quadrants around the tumor. During the neck dissection, levels I-IV were measured for fluorescence using the Mini-FLARE imaging system. RESULTS: In all 10 patients, NIR fluorescence imaging enabled visualization of one or more SLNs. A total of 17 SLNs were identified. The mean contrast between the fluorescent signal of the lymph nodes and of the surrounding tissue was 8.7±6.4. In 3 patients, of which 1 was false-negative, lymph node metastases were found. After administration of ICG:HSA, the average number of fluorescent lymph nodes significantly increased over time (P<0.001). CONCLUSION: This study demonstrated feasibility to detect draining lymph nodes in head and neck cancer patients using NIR fluorescence imaging. However, the fluorescent tracer quickly migrated beyond the SLN to higher tier nodes.